Table 3 Contributing risk factors for Oral Submucous Fibrosis

Chewing smokeless tobacco

Dip, Snuff, Snus and chewing tobacco have been reported as major contributing factors [34, 35, 39, 40].

Nutritional

Deficiencies of iron, folate & vitamin B12 result in mucosal atrophy, notably in the mouth. Increased levels of iron enhance hydroxylation of proline and lysine in the process of collagen synthesis [40].

Chilies

Hypersensitivity reactions to capsaicin might contribute to fibrosis [41,42,43].

Toxic levels of copper

Copper upregulates the enzyme lysyl oxidase, enhancing cross linking of collagen and elastin [35, 44, 45].

Genetic predisposition

HLA-A10, HLA-B7, HLA-DR3, haplotypes A10/DR3, B3/DR3 and A10/B8 are found in increased frequency in OSMF patients [45].

Immunological predisposition

Subjects with high endogenous expression of CD4 and HLA-DR on lymphocytes and Langerhans cells may have dysregulation of their immune-inflammatory response with bystander tissue injury [45].